Target Information
Target General Infomation | |||||
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Target ID |
T97071
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Former ID |
TTDS00441
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Target Name |
Glutamate carboxypeptidase II
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Gene Name |
FOLH1
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Synonyms |
FGCP; Folate hydrolase 1; Folylpoly-gamma-glutamate carboxypeptidase; MGCP; Membrane glutamate carboxypeptidase; N-acetylated-alpha-linked acidic dipeptidase I; NAALADase I; PSM; PSMA; Prostate-specific membrane antigen; Pteroylpoly-gamma-glutamate carboxypeptidase; FOLH1
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Target Type |
Successful
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Disease | Brain injury [ICD10: S09.90] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Influenza virus [ICD10: J11.1] | |||||
Metastatic prostate cancer; Non-metastatic prostate cancer [ICD9: 140-229, 185; ICD10: C61] | |||||
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0] | |||||
Prostate cancer [ICD9: 185; ICD10: C61] | |||||
Prostate cancer diagnosis [ICD9: 140-229, 185; ICD10: C61] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
Has both folate hydrolase and n-acetylated-alpha-linked- acidic dipeptidase (naaladase) activity. Has a preference for tri- alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission.
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BioChemical Class |
Peptidase
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Target Validation |
T97071
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UniProt ID | |||||
EC Number |
EC 3.4.17.21
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Sequence |
MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLFGWFIKSSNEATNITPKHNMKA
FLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFGLDSVELAHYDVLLSYP NKTHPNYISIINEDGNEIFNTSLFEPPPPGYENVSDIVPPFSAFSPQGMPEGDLVYVNYA RTEDFFKLERDMKINCSGKIVIARYGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVK SYPDGWNLPGGGVQRGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYY DAQKLLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTRIYNVIG TLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGTLKKEGWRPRRTILFAS WDAEEFGLLGSTEWAEENSRLLQERGVAYINADSSIEGNYTLRVDCTPLMYSLVHNLTKE LKSPDEGFEGKSLYESWTKKSPSPEFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKN WETNKFSGYPLYHSVYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDY AVVLRKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFDKSNPIV LRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGESFPGIYDALFDIESKVD PSKAWGEVKRQIYVAAFTVQAAAETLSEVA |
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Structure |
1Z8L; 2C6C; 2C6G; 2C6P; 2CIJ; 2JBJ; 2JBK; 2OOT; 2OR4; 2PVV; 2PVW; 2XEF; 2XEG; 2XEI; 2XEJ; 3BHX; 3BI0; 3BI1; 3BXM; 3D7D; 3D7F; 3D7G; 3D7H; 3IWW; 3RBU; 3SJE; 3SJF; 3SJG; 3SJX; 4JYW; 4JZ0; 4LQG; 4MCP; 4MCQ; 4MCR; 4MCS; 4NGM; 4NGN; 4NGP; 4NGQ; 4NGR; 4NGS; 4NGT; 4OC0; 4OC1; 4OC2; 4OC3; 4OC4; 4OC5; 1Z8L; 2C6C; 2C6G; 2C6P; 2CIJ; 2JBJ; 2JBK;2OOT; 2OR4; 2PVV; 2PVW; 2XEF; 2XEG; 2XEI; 2XEJ; 3BHX; 3BI0; 3BI1; 3BXM; 3D7D; 3D7F; 3D7G; 3D7H; 3IWW; 3RBU; 3SJE; 3SJF; 3SJG; 3SJX; 4JYW; 4JZ0; 4LQG; 4MCP; 4MCQ; 4MCR; 4MCS; 4NGM; 4NGN; 4NGP; 4NGQ; 4NGR; 4NGS; 4NGT; 4OC0; 4OC1; 4OC2; 4OC3; 4OC4; 4OC5
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Drugs and Mode of Action | |||||
Drug(s) | Capromab | Drug Info | Approved | Prostate cancer diagnosis | [1], [2], [3] |
99mTc-MIP-1404 | Drug Info | Phase 2 | Prostate cancer | [4] | |
ATL101 | Drug Info | Phase 2 | Influenza virus | [5] | |
G-202 | Drug Info | Phase 2 | Solid tumours | [6] | |
J 591 Lu-177 | Drug Info | Phase 2 | Metastatic prostate cancer; Non-metastatic prostate cancer | [7] | |
MLN-591RL | Drug Info | Phase 2 | Prostate cancer | [8] | |
MLN-2704 | Drug Info | Phase 1/2 | Prostate cancer | [9] | |
99mTc-MIP-1405 | Drug Info | Phase 1 | Prostate cancer | [10] | |
Autologous T-cell therapy | Drug Info | Phase 1 | Prostate cancer | [11] | |
BAY-1075553 | Drug Info | Phase 1 | Prostate cancer | [12] | |
GPI-16072 | Drug Info | Phase 1 | Neuropathic pain | [13] | |
Iofolastat I-124 | Drug Info | Phase 1 | Prostate cancer | [14] | |
MT-112 | Drug Info | Phase 1 | Solid tumours | [15] | |
PSMA subunit vaccine | Drug Info | Phase 1 | Prostate cancer | [16] | |
PSMA-targeted tubulysin B conjugates | Drug Info | Phase 1 | Prostate cancer | [17] | |
PSMA-VRP | Drug Info | Phase 1 | Prostate cancer | [18] | |
IRX-4 | Drug Info | Preclinical | Prostate cancer | [19] | |
MDX-070 | Drug Info | Discontinued in Phase 2 | Prostate cancer | [20] | |
2-PMPA | Drug Info | Terminated | Discovery agent | [21] | |
Inhibitor | 2-(2-carboxy-5-mercaptopentyl)benzoic acid | Drug Info | [22] | ||
2-(2-carboxy-7-mercaptoheptyl)benzoic acid | Drug Info | [22] | |||
2-(2-Hydroxycarbamoyl-ethyl)-pentanedioic acid | Drug Info | [23] | |||
2-(2-Mercapto-ethyl)-pentanedioic acid | Drug Info | [24] | |||
2-(2-Phosphonooxy-ethyl)-pentanedioic acid | Drug Info | [24] | |||
2-(3-carbamoylbenzyl)-5-mercaptopentanoic acid | Drug Info | [22] | |||
2-(3-carboxybenzyl)succinic acid | Drug Info | [22] | |||
2-(3-cyanobenzyl)-5-mercaptopentanoic acid | Drug Info | [22] | |||
2-(3-Hydroxycarbamoyl-propyl)-pentanedioic acid | Drug Info | [23] | |||
2-(3-Mercapto-propyl)-pentanedioic acid | Drug Info | [24] | |||
2-(3-Methylsulfanyl-propyl)-pentanedioic acid | Drug Info | [24] | |||
2-(4-Mercapto-butyl)-pentanedioic acid | Drug Info | [24] | |||
2-(5-Mercapto-pentyl)-pentanedioic acid | Drug Info | [24] | |||
2-(phosphonomethyl)pentanedioic acid | Drug Info | [25] | |||
2-benzyl-5-mercaptopentanoic acid | Drug Info | [22] | |||
2-Hydroxycarbamoyl-pentanedioic acid | Drug Info | [23] | |||
2-Hydroxycarbamoylmethyl-pentanedioic acid | Drug Info | [23] | |||
2-Mercapto-pentanedioic acid | Drug Info | [24] | |||
2-Mercaptomethyl-pentanedioic acid | Drug Info | [24] | |||
2-Phosphonooxy-pentanedioic acid | Drug Info | [24] | |||
2-PMPA | Drug Info | [26] | |||
3-(1-carboxy-4-mercaptobutoxy)benzoic acid | Drug Info | [22] | |||
3-(2-carbamoyl-5-mercaptopentyl)benzoic acid | Drug Info | [22] | |||
3-(2-carboxy-3-mercaptopropyl)benzoic acid | Drug Info | [22] | |||
3-(2-carboxy-3-phosphonopropyl)benzoic acid | Drug Info | [22] | |||
3-(2-carboxy-4-mercaptobutyl)benzoic acid | Drug Info | [22] | |||
3-(2-carboxy-5-mercaptopentyl)benzoic acid | Drug Info | [22] | |||
3-(2-carboxy-6-mercaptohexyl)benzoic acid | Drug Info | [22] | |||
3-[(1-carboxy-4-mercaptobutyl)thio]benzoic acid | Drug Info | [22] | |||
4-(2-carboxy-5-mercaptopentyl)benzoic acid | Drug Info | [22] | |||
5-Mercapto-pentanoic acid | Drug Info | [24] | |||
compound 8d | Drug Info | [27] | |||
G-202 | Drug Info | [28] | |||
GPI-16072 | Drug Info | [29] | |||
Iofolastat I-124 | Drug Info | [30] | |||
MIP-1375 | Drug Info | [31] | |||
PGI-02749 | Drug Info | [31] | |||
QUISQUALATE | Drug Info | [32] | |||
Modulator | 99mTc-MIP-1340 | Drug Info | [31] | ||
99mTc-MIP-1404 | Drug Info | [33] | |||
99mTc-MIP-1405 | Drug Info | [33] | |||
ATL101 | Drug Info | [34] | |||
BAY-1075553 | Drug Info | [35] | |||
CTT-54 | Drug Info | [31] | |||
J 591 Lu-177 | Drug Info | [7] | |||
MDX-1147 | Drug Info | [31] | |||
PSMA-targeted tubulysin B conjugates | Drug Info | [36] | |||
Immunomodulator (Immunostimulant) | IRX-4 | Drug Info | [37] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Alanine, aspartate and glutamate metabolism | ||||
Metabolic pathways | |||||
Vitamin digestion and absorption | |||||
NetPath Pathway | TCR Signaling Pathway | ||||
TNFalpha Signaling Pathway | |||||
Reactome | Amino acid synthesis and interconversion (transamination) | ||||
WikiPathways | One Carbon Metabolism | ||||
References | |||||
REF 1 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (BLA) 103608. | ||||
REF 2 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6878). | ||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | ||||
REF 4 | ClinicalTrials.gov (NCT01667536) A Phase 2 Diagnostic Imaging Study With 99mTc-MIP-1404 in Men With High-Risk Prostate Cancer Scheduled for Radical Prostatectomy (RP) and Extended Pelvic Lymph Node Dissection (EPLND) Compared to Histopathology. U.S. National Institutes of Health. | ||||
REF 5 | Clinical pipeline report, company report or official report of Atlab pharma. | ||||
REF 6 | ClinicalTrials.gov (NCT01777594) Study of G-202 as Second-Line Therapy Following Sorafenib in Hepatocellular Carcinoma. U.S. National Institutes of Health. | ||||
REF 7 | Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013 Sep 15;19(18):5182-91. | ||||
REF 8 | ClinicalTrials.gov (NCT00195039) Treatment With Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Metastatic Prostate Cancer. U.S. National Institutes of Health. | ||||
REF 9 | ClinicalTrials.gov (NCT00070837) MLN2704 in Subjects With Metastatic Androgen-Independent Prostate Cancer. U.S. National Institutes of Health. | ||||
REF 10 | ClinicalTrials.gov (NCT01261754) A Study of 99mTc-MIP-1404 and 99mTc-MIP-1405 in Patients With Metastatic Prostate Adenocarcinoma and Healthy Volunteers. U.S. National Institutes of Health. | ||||
REF 11 | Clinical application of genetically modified T cells in cancer therapy. Clin Transl Immunology. 2014 May 16;3(5):e16. doi: 10.1038/cti.2014.7. eCollection 2014. | ||||
REF 12 | Phase I Study: BAY 1075553 PET/CT in Staging and Re - Staging of Prostate Cancer Patients - Comparison with 18F-Choline PET/CT. World Molecular Imaging Society. September 20, 2013 | ||||
REF 13 | Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. | ||||
REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026421) | ||||
REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031326) | ||||
REF 16 | Clinical pipeline report, company report or official report of Alphavax. | ||||
REF 17 | J Clin Oncol 33, 2015 (suppl; abstr e13527) | ||||
REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012200) | ||||
REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026363) | ||||
REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015769) | ||||
REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009714) | ||||
REF 22 | J Med Chem. 2006 May 18;49(10):2876-85.Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain. | ||||
REF 23 | Bioorg Med Chem Lett. 2003 Jul 7;13(13):2097-100.Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate carboxypeptidase II. | ||||
REF 24 | J Med Chem. 2003 May 8;46(10):1989-96.Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor. | ||||
REF 25 | Bioorg Med Chem. 2008 Feb 15;16(4):1648-57. Epub 2007 Nov 17.Design and synthesis of a siderophore conjugate as a potent PSMA inhibitor and potential diagnostic agent for prostate cancer. | ||||
REF 26 | Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat Med. 1999 Dec;5(12):1396-402. | ||||
REF 27 | Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents. J Med Chem. 2004 Mar 25;47(7):1729-38. | ||||
REF 28 | National Cancer Institute Drug Dictionary (drug id 666090). | ||||
REF 29 | Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. | ||||
REF 30 | 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med. 2011 Jul;52(7):1087-93. | ||||
REF 31 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1606). | ||||
REF 32 | J Med Chem. 2007 Jul 12;50(14):3267-73. Epub 2007 Jun 14.Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II. | ||||
REF 33 | 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med. 2013 Aug;54(8):1369-76. | ||||
REF 34 | Clinical pipeline report, company report or official report of Atlab pharma. | ||||
REF 35 | Preclinical evaluation of BAY 1075553, a novel (18)F-labelled inhibitor of prostate-specific membrane antigen for PET imaging of prostate cancer. Eur J Nucl Med Mol Imaging. 2014 Jan;41(1):89-101. | ||||
REF 36 | Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand. Mol Pharm. 2009 May-Jun;6(3):780-9. | ||||
REF 37 | Irx4 identifies a chamber-specific cell population that contributes to ventricular myocardium development. Dev Dyn. 2014 Mar;243(3):381-92. |
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